GSTT4 – Velocardiofacial Syndrome

This summary describes the association between GSTT4 and velocardiofacial syndrome. The evidence supporting this relationship is derived from a single study reporting a 125 kb microdeletion in a patient with typical features of 22q11 deletion syndrome, including velopharyngeal insufficiency, splenomegaly, immunodeficiency, and thrombocytopenia (PMID:29465581). In this study, GSTT4 is one of eight candidate genes within the deleted region, suggesting a potential contribution through haploinsufficiency. Although the patient’s phenotype aligns with velocardiofacial syndrome, the evidence for GSTT4 as an independent driver is limited by the absence of additional unrelated probands or segregation data. The study did not provide specific molecular variants for GSTT4 in an HGVS‐compliant format, and the candidate status is inferred solely from the deletion encompassing multiple genes.

The genetic evidence is categorized as Limited based on the single case report and the lack of isolated variant-specific data, with the candidate gene being identified as part of a larger contiguous deletion (PMID:29465581). Functional evidence is also considered Limited because no experimental studies have directly assessed the role of GSTT4 in the disease process. Overall, while GSTT4 remains a compelling candidate given its loss in a patient with a classical velocardiofacial syndrome presentation, further evidence through additional cases, segregation analysis, and experimental validation is needed to firmly establish its role.

Key Take‑home: GSTT4’s inclusion in the 125 kb deletion linked to velocardiofacial syndrome highlights its potential relevance to the phenotype, yet the current evidence is insufficient for strong diagnostic or commercial application without further validation.

References

• Medicine • 2018 • Atypical microdeletion in 22q11 deletion syndrome reveals new candidate causative genes: A case report and literature review PMID:29465581

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